Rapid selection of P323L in the SARS-CoV-2 polymerase (NSP12) in humans and non-human primate models and confers a large plaque phenotype

The mutational landscape of SARS-CoV-2 varies at both the dominant viral genome sequence and minor genomic variant population. An early change associated with transmissibility was the D614G substitution in the spike protein. This appeared to be accompanied by a P323L substitution in the viral polymerase (NSP12), but this latter change was not under strong selective pressure. Investigation of P323L/D614G changes in the human population showed rapid emergence during the containment phase and early surge phase of wave 1 in the UK. This rapid substitution was from minor genomic variants to become part of the dominant viral genome sequence. A rapid emergence of 323L but not 614G was observed in a non-human primate model of COVID-19 using a starting virus with P323 and D614 in the dominant genome sequence and 323L and 614G in the minor variant population. In cell culture, a recombinant virus with 323L in NSP12 had a larger plaque size than the same recombinant virus with P323. These data suggest that it may be possible to predict the emergence of a new variant based on tracking the distribution and frequency of minor variant genomes at a population level, rather than just focusing on providing information on the dominant viral genome sequence e.g., consensus level reporting. The ability to predict an emerging variant of SARS-CoV-2 in the global landscape may aid in the evaluation of medical countermeasures and non-pharmaceutical interventions.

Characteristics of Pruritus in Various Clinical Variants of Psoriasis: Results of the Multinational, Multicenter, Cross-Sectional Study

Psoriasis is a chronic, inflammatory skin disease present in about 3% of the world’s population. The clinical symptoms manifest diversely, therefore one can distinguish several subtypes of psoriasis. The majority of patients with psoriasis experience pruritus, which is an unpleasant sensation that decreases patients’ quality of life. The knowledge on pruritus in different subtypes of psoriasis is limited. We have performed a cross-sectional, prospective, and multicenter study to evaluate the relationship between clinical subtypes of psoriasis (large-plaque, nummular, guttate, palmoplantar, inverse, erythrodermic, palmoplantar pustular, generalized pustular psoriasis, and psoriasis of the scalp) and the prevalence, intensity, and clinical manifestation of itch. We introduced a questionnaire assessing various aspects of pruritus to a total of 254 patients. Out of these, 42 were excluded. Pruritus was present in 92.9% of the remaining patients and its prevalence did not depend on the clinical subtype. A correlation between the severity of psoriasis and the intensity of itch was explicitly noticeable in palmoplantar pustular psoriasis and scalp psoriasis (p < 0.05). The itch sensation was individual and differed among subtypes of psoriasis. In conclusion, pruritus is a frequent phenomenon, and its presentation is different in various subtypes of psoriasis.

A new principle for the diagnosis morphea in the onset of the disease

BACKGROUND: Because of the low specificity morphea clinical manifestations in early stages, the differential diagnosis is difficult. AIMS: The purpose of the research is to propose a new diagnostic method for early stages of localized scleroderma. MATERIALS AND METHODS: During 20112020, 77 patients with clinical manifestations of morphea and 127 controls were examined and included in the study at the LenOblCenter. All participants were conducted a transcutaneous oximetry with the TCM-400 Radiometer apparatus. The tissue oxygen perfusion (tcpO2) level from 40 to 50 mm Hg was considered as a reversible decrease, from 30 to 40 mm hg was a borderline decline and the value below 30 mm hg was critical. The following diagnostic skin biopsy was conducted in all 77 patients RESULTS: Skin biopsy allowed to form 4 research groups: 40 patients with morphea, 12 patients with granuloma annulare, 15 patients with small plaque parapsoriasis and 10 individuals with large plaque parapsoriasis. 7 (17.5%) patients with morphea had normal tcpO2 values, 9 (22.5%) patients had significant decrease of tcpO2, 24 patients (60%) showed a reversible decrease of tcpO2. 3/12 (25%) patients with granuloma annulare and 1 patient (10%) with large plaque parapsoriasis had minor oxygen level decrease. Measurement on the healthy skin showed tcpO2 decrease in patients with comorbidities ― 3/77 (3.9%) in research group and 28/127 (22%) in controls. CONCLUSIONS: Transcutaneous oximetry is a new perspective direction in the diagnostic algorithm of the morphea based on the pathogenesis and morphological features of the disease.

The great imitator: A rare presentation of annular and corymbose secondary syphilis

A corymbose (or corymbiform) arrangement in secondary syphilis (derived from the Greek word korymbos) is characterised by a central large plaque or papule surrounded by smaller satellite lesions akin to an explosion, whereas annular plaques consist of a peripheral ring of erythematous papules with central hyperpigmentation. These are very rare cutaneous manifestations of secondary syphilis. This case report focuses on one such interesting case which presented with the annular and corymbose pattern involving the face and genitalia.

From Benign Inflammatory Dermatosis to Cutaneous Lymphoma. DNA Copy Number Imbalances in Mycosis Fungoides versus Large Plaque Parapsoriasis

Background and Objectives: Mycosis fungoides (MF) and large plaque parapsoriasis (LPP) evolution provide intriguing data and are the cause of numerous debates. The diagnosis of MF and LPP is associated with confusion and imprecise definition. Copy number alterations (CNAs) may play an essential role in the genesis of cancer out of genes expression dysregulation. Objectives: Due to the heterogeneity of MF and LPP and the scarcity of the cases, there are an exceedingly small number of studies that have identified molecular changes in these pathologies. We aim to identify and compare DNA copy number alterations and gene expression changes between MF and LPP to highlight the similarities and the differences between these pathologies. Materials and Methods: The patients were prospectively selected from University Clinic of Dermatology and Venereology Timișoara, Romania. From fresh frozen skin biopsies, we extracted DNA using single nucleotide polymorphism (SNP) data. The use of SNP array for copy number profiling is a promising approach for genome-wide analysis. Results: After reviewing each group, we observed that the histograms generated for chromosome 1–22 were remarkably similar and had a lot of CNAs in common, but also significant differences were seen. Conclusions: This study took a step forward in finding out the differences and similarities between MF and LPP, for a more specific and implicitly correct approach of the case. The similarity between these two pathologies in terms of CNAs is striking, emphasizing once again the difficulty of approaching and differentiating them.

A case report of psoriasis exacerbation following COVID-19

The article presents a clinical case of severe exacerbation of psoriasis after a novel coronavirus infection. A 60 years old patient who has recovered from Corona Virus Disease 2019 (COVID-19) was admitted to the Republican Skin and Venereal Disease Dispensary of the Republic of Tatarstan for inpatient treatment with a diagnosis Large plaque psoriasis involving palms and soles. Progressive stage. Scalp psoriasis. Nail psoriasis. This was the first time the patient had experienced psoriasis exacerbation of this severity in his medical history. Presumably, exacerbation of psoriasis was due to the use of hydroxychloroquine. The exacerbation of psoriasis during the pandemic outbreak of Coronavirus disease can be explained by the following reasons: use of hydroxychloroquine, excessive inflammatory response to COVID-19, psychological stress, anxiety, depression, the decline in household income, limited outdoor activities. It is necessary to focus attention of physicians to the fact that patients who have suffered from COVID-19 may develop exacerbation of psoriasis.

Ayurved for Skin Disorders, A Clinical Success Story of Guttate Psoriasis

Psoriasis is a chronic inflammatory papulo-squamous disorder of skin characterized by sharply defined erythematous-squamous lesion varying from pinpoint to large plaque, affecting 1-3% of population worldwide. Psoriasis is well known for its course of remission and exacerbation. Here we report a case of 14-year-oldmale 42 kg weight, rotund physique child, diagnosed as Guttate psoriasis, Guttate psoriasis can be closely correlated with Ekkushtha (one of subtype of Kustha) in Ayurveda. Management of patient with, shodhan therapy (Biological purification of body) like mriduvirechan (Mild laxative) and shaman therapy (conservative therapy) showed remarkable improvement in patient condition. There is appreciable psychological health impairment found in patient, which adversely affect patient quality of life. This case study shows that Ayurveda line of treatment (Shodhan and shaman) gives significant result in the treatment of Guttate psoriasis.

Effect of Urban Fringes Green Space Fragmentation on Ecosystem Service Value

In this study, an urban fringe green space classification system was established to explore the spatiotemporal variation of green space landscape and ecosystem service value (ESV) based on multi-source land-use data of Ganjingzi district from 2000 to 2018. (1) Results show that the total green space area declined from 359.57 to 213.46 km 2 over the study period. Green space large plaque index (LPI) and class area both gradually declined, whereas the number of plaques (NP) and plaque density (PD) gradually increased, indicating green space landscape fragmentation. (2) Additionally, the value of green space ecosystem services reduced from 397.42 to 124.93 million yuan. The dynamic degree of ESV change in green space increased or decreased moderately, always being < 0 and showing a decreasing trend of ESV. From a spatial variation perspective, dynamic degrees of ESV variation in the western and northern regions with relatively intensive green space were higher than those in the east. Regarding ESV of various green space types, forest land had the highest functional values of ecological regulation and support, whereas arable land provided the highest functional values of production supply. (3) The ecological service function value of green space system is negatively correlated with PD, NP, edge density, landscape shape index, and Shannon’s diversity index, and positively correlated with aggregation index, contagion metrics, and LPI. The correlation coefficient between the climate regulation function of forest and the change of number of plaques is -0.874. The correlation coefficient of the recreation and culture of the wetland to the plaque density change is no less than -0.214.

Loss of the vaccinia virus 35-amino acid hydrophobic O3 protein is partially compensated by mutations in the transmembrane domains of other entry proteins

Eleven highly conserved proteins comprise the poxvirus entry-fusion complex (EFC). We focused on vaccinia virus (VACV) O3, a 35-amino acid, largely hydrophobic component of unknown specific function. Experimental evolution was carried out by blindly passaging a virus that was severely impaired in entry due to deletion of the gene encoding O3. Large plaque variants that arose spontaneously were discerned by round four and their numbers increased thereafter. Genome sequencing of individual cloned viruses revealed mutations in predicted transmembrane domains of three open reading frames encoding proteins with roles in entry. There were frame-shift mutations in consecutive Ts in open reading frames F9L and D8L and a nonsynonymous base substitution in L5R. F9 and L5 are EFC proteins and D8 is involved in VACV cell attachment. The F9L mutation occurred by round four in each of three independant passages, whereas the L5R and D8L mutations were detected only after nearly all of the genomes already had the F9L mutation. Viruses with deletions of O3L and single or double F9L, L5R and D8L mutations were constructed by homologous recombination. In a single round of infection, viruses with adaptive mutations including F9L alone or in combination exhibited statistically significant higher virus titers than the parental O3L deletion mutant or the L5R or D8L mutants, consistent with the order of selection during the passages. Further analyses indicated that the adaptive F9L mutants also had higher infectivities, entered cells more rapidly and increased EFC assembly, which partially compensated for the loss of O3. IMPORTANCE Entry into cells is an essential first step in virus replication and an important target of vaccine- elicited immunity. For enveloped viruses, this step involves the fusion of viral and host membranes to form a pore allowing entry of the genome and associated proteins. Poxviruses are unique in that this function is mediated by an entry-fusion complex (EFC) of eleven transmembrane proteins rather than by one or a few. The large number of proteins has hindered investigation of their individual roles. We focused on O3, a predominantly hydrophobic 35 amino acid component of the vaccinia virus EFC, and found that spontaneous mutations in the transmembrane domains of certain other entry proteins can partially compensate for the absence of O3. The mutants exhibited increased infectivity, entry and assembly or stability of the EFC.